Predictions in this field are particularly dangerous, on the
basis of a history that is dense with surprises in nearly all facets of the
discipline. For example, Ebola was most everyone's choice for medical story of
the year for 2014, but this infection was barely on the radar screen 1 year
ago.

The influenza vaccine recommended for the current epidemic
was created for the anticipated H1N1 strain, but the influenza now causing
widespread disease is largely the H3N2 strain. Chikungunya is hard to pronounce
and was rarely seen until the enormous epidemic in the Caribbean that spilled
over to the United States in returning travelers—and, more worrisome, it
achieved endemic transmission by mosquitoes in Florida.

Antibiotic resistance has been a notorious concern for more
than a decade, but 2014 brought federal legislation (the President's Council of
Advisors on Science and Technology report[1]) signed by executive order to
address the problem, with a $1.1 billion price tag that came to most as a
surprise. For years, we lamented that there were no new antibiotics, and
suddenly we have four.

With this rather humble disclaimer, the following are
predictions for the field of infectious diseases for 2015.

Ebola

The epidemic in West Africa is devastating and tragic, but
sustained endemic transmission in the United States and other developed
countries is very unlikely. This is the assessment of an acknowledged leader in
the field, Dr Peter Piot,[2] who co-discovered the virus in 1976.[3]

The difference in outcomes in the United States vs West
Africa is the healthcare environment in West Africa, where there is a long
history of civil wars, lack of a healthcare system, a paucity of providers,
burial and religious practices that promote transmission, and chaotic
healthcare administration, highlighted in an extensive review in the December
29, 2014, New York Times.[4] These conditions do not exist in developed
countries, so Ebola seems likely to be limited to the occasional case
transferred from West Africa.

The 35 designated Ebola centers in the United States (for
which $6 billion has been allocated) will probably be unnecessary and be
justified as centers for emerging contagious diseases. This scenario is
reminiscent of the federal response to bioterrorism in 2001 that prompted the
creation of a bioweapon defense funding source and multiple academic
bioterrorism centers. The lack of a subsequent bioweapon threat resulted in the
diversion of the mission of these resources.

For Africa, the epidemic seems to need better coordination
between agencies that are on the ground, but it looks as though progress is
being made, especially in Nigeria. A vaccine seems probable.

Antibiotic Resistance

The alarming crisis of antibiotic resistance was predicted
by the Infectious Diseases Society of America (IDSA) in 2004 and has now become
a recognized crisis by the Centers for Disease Control and Prevention (CDC),
the World Health Organization, and President Obama. Its genesis is simple: vast
use and abuse, leading to microbial resistance by Mendelian laws and a
reduction in antibiotic development that previously kept us ahead.

The resistance genes have been traced back 3.5 million
years,[5] long before human life, and the paucity of new antibiotics is simply
a product of economic and regulatory realities: Antibiotics are short-course
and historically cheap compared with other drug classes, and they are the only
drugs that lose potency with excessive use.[6]

Recognizing the frightening consequences of the
"postantibiotic era," there is now progress, with incentives for new
drug development and diminished US Food and Drug Administration (FDA)
regulatory hurdles.[7] The result has been reentry into the market by major
pharmaceutical companies, such as Merck, and several new smaller companies that
have seen this as a niche market opportunity,[7] prompting a modest surge in
new antibiotics.

It is anticipated that this progress will continue in 2015,
but the challenge is substantial, owing to the extent of the problem, the cost
of new drug development (now estimated at $2 billion), and the stronger
attraction of drugs that are taken for decades (such as statins) or those with
the price tags of cancer chemotherapeutics.

The attempt to salvage antibiotics also requires efforts to
deter unnecessary use. The President's PCAST report includes nine categories of
response, but two are especially important to practitioners.[8,9] First is a
comprehensive surveillance system that is combined with whole-gene sequencing
and global connections. This may prove very useful for informing intervention
efforts, especially those involving infection control.

The second important component is the requirement for an
antibiotic stewardship program in every hospital as a Centers for Medicare
& Medicaid Services (CMS) condition of payment. This is potentially great
news, but there is no timetable and no definition of "antibiotic
stewardship." Under total government control, however, it could deter
alternative efforts.

At this point, for 2015, it seems best to encourage
compliance, but to also march ahead with local planning. Resistance is a crisis
with immediate needs.

New Antibiotics

2015 will see the introduction or expanded use of three
antistaphylococcal agents:

• Tedizolid (Sivextro®), an agent similar to linezolid, with
the advantages of once-daily administration, cost advantages, and possibly
fewer side effects;

• Dalbavancin (Dalvance™), a parenteral lipoglycopeptide
with a vancomycin-like spectrum but a half-life of 6 days, permitting a total
regimen for most skin and soft-tissue infections with two doses separated by 7
days; and

• Oritavancin (Orbactiv™), another long half-life
lipoglycopeptide that provides a total 2-week course with a single intravenous
dose.[10]

These three agents share the advantage of potential for
outpatient management or early hospital discharge for selected staphylococcal
infections.

The big challenge is new drugs for infections involving
gram-negative bacilli. Recent progress is the FDA approval of
ceftolozane/tazobactam (Zerbaxa™), a novel antipseudomonal cephalosporin with a
well-established beta-lactamase inhibitor that has activity against extended
spectrum beta-lactamase–producing Enterobacteriaceae and some highly resistant
Pseudomonas aeruginosa. [11] This recent progress after a long drought is
welcome and would appear to predict continued development of urgently needed
drugs.

Hospital-Associated
Infections

In 2015, emphasis will be on hospital-associated infections,
with demands to address the problem and substantial financial consequences
levied by CMS on the basis of institutional performance. A major concern in the
US healthcare system is to reduce rates of healthcare-associated infection,
with annual costs now calculated at $23 billion and 115,000 deaths per
year.[12]

The hospital setting is now recognized as posing
unacceptable risks for infection, and substantial efforts are under way to
identify alternative settings for healthcare. This concern is national and, in
fact, international. For example, health authorities in the United Kingdom
recently recommended home delivery as being suitable for low-risk multiparous
pregnant women, "because the rate of interventions is lower"[13]
(thereby reducing the risk for nosocomial infection).

For the practitioner, the focus for infection reduction is
on "the big five":

These five infections account for 80% of nosocomial
infections, and they will now be audited and incur payment penalties by
CMS.[12] At the operational level, this means that hospital administrators will
need to support efforts to reduce nosocomial infections, with particular
emphasis on these five infections.

Microbiome

This is the subject of a large National Institutes of
Health-sponsored initiative, with funding of 27 centers at about $180 million
per year to define the microbiome in health and disease.[14] The good news is
that many justifiably see this as one of the most exciting and potentially
transforming areas of biomedical research. The bad news is that to date, there
are lots of reports, but nothing yet to take to the clinic.

What we do know from studies in experimental animals, and
some in adults, is that human life is incredibly complex. There is a unique
flora in each organ system; this flora is generally easy to manipulate with
antibiotics; the constituents are largely organisms not encountered in clinical
laboratories; and most are extremely fastidious, so they can't be grown in
clinical laboratories. We also know that currently available probiotics play no
clearly established role in clinical care (with the possible exception of
preventing antibiotic-associated diarrhea).

Many associations have been established between the
microbiome and such disease states as inflammatory bowel disease, obesity,
diabetes, autoimmune disease, the metabolic syndrome, cancer, and
atherosclerosis. The hope is that the flora can be manipulated with antibiotics
or probiotics to improve health. This is supported by some promising data
showing that manipulation of the gut flora with antibiotics can have an impact
on markers of atherosclerosis.[15]

The most promising immediate application is stool transplant
for relapsing CDI. This treatment is now more than five decades old and has a
relatively small following of long-term enthusiasts, but finally seems ready
for prime time.

Vaccines

These products, like antibiotics, are the major weaponry of
infectious disease management and prevention, especially for viral pathogens.
In terms of new products, it appears likely that 2015 will bring a universal
vaccine that includes all four viral agents of dengue,[16] and an Ebola vaccine
is a high priority and a likely success.[17]

Further back are two C difficile vaccine products (from
Sanofi and Pfizer); both of these are in 15,000-patient trials, and the Pfizer
product has an FDA "fast-track" designation.[18] This situation
merits watching, although these vaccines will not be available in 2015.

Gene Sequencing

This method of establishing transmission patterns appears to
be almost ready for widespread use in many hospitals for infection control.
Testimony to its utility is its use for defining risk for CDI in the United
Kingdom,[19] and for informing infection control in the devastating outbreak of
infections involving carbapenemase-producing Klebsiella pneumoniae.[20] This
technology has become increasingly affordable, necessary, and available, so
expanded use in large centers is likely in 2015. This work seems to
revolutionize some of the current concepts of nosocomial infections.

Stool Transplant

Fecal microbiota transplant (FMT) is now recognized as the
best answer to the challenge of managing repeated relapses of CDI. Most trials
show good results with stool acquired from properly screened donors that is
then inserted by enema, endoscope, or nasogastric tube. Some clinicians use
OpenBiome (Medford, Massachusetts) as the source for screened stool, which is
stored in a frozen state and available commercially for $250 per specimen.[21]

More recent data also support the use of capsules containing
stool that are delivered by mouth. A recent review concludes that this is the
most clinically effective and cost-effective approach for managing relapsing
CDI.[22]

FMT is highlighted here because it is new, practical for
general use, and cost-effective (if you avoid endoscopy), and it demonstrates
nicely the first and possibly only application of the microbiome project.
Consequently, it seems clear that 2015 will see substantial increased use of
FMT, with debates about the insertion method: capsule, nasogastric tube,
endoscope, or enema. A more challenging issue is the possible long-term health
consequences of ingesting someone else's colonic flora, assuming it is retained
in whole or in part.

Epidemics

We know that there will be epidemics, but the mystery is
what type and where. Particularly concerning from 2014 is chikungunya, with
> 600,000 cases in the Caribbean and 240 cases in the United States,
including some that were not related to travel; this indicates that mosquito
transmission is taking place in Florida, where chikungunya seems likely to
become endemic.[23] Dengue is a similar problem, and both diseases are
associated with extraordinary morbidity.

A long-term follow-up of patients with chikungunya acquired
during an outbreak on Réunion showed that symptoms, including arthritic
complaints, persisted for longer than 2 years in 30% of affected persons.[24]
Both of these viral infections carry substantial morbid consequences and are
likely to be endemic in Southern states, especially Texas and Florida.

The other unexpected and even more devastating new epidemic
is enterovirus D68. This virus causes severe and sometimes fatal respiratory
infections or a polio-like illness in children.[25]

We can also expect periodic outbreaks of measles, mumps,
pertussis, and norovirus and other foodborne infections. These are all
anticipated for 2015, and although time and place cannot be predicted, all are
important in terms of rapid detection for management, reporting, and public
health response.

Expectations for 2015 That Will Have the Most Impact on
Providers

• Antibiotic resistance: There will be great emphasis on
antibiotic conservation—short-course, molecular diagnostics for antibiotic
selection, use of procalcitonin to guide when to start and stop antibiotics,
use of automatic stop orders, early intravenous-to-oral switch (leading to
quicker hospital discharges), and avoidance of unnecessary antibiotics for
upper respiratory infections and bronchitis.

• Enhanced concern about infection control: Particular
emphasis will be placed on "the big 5" that account for 80% of
nosocomial infections and will be audited by CMS—ventilator-associated
pneumonia, surgical-site infection (primarily after colonic surgery and
hysterectomy), CDI, primary bacteremia (especially central line-associated
bloodstream infection), and catheter-associated urinary tract infection.

• Increased use of molecular diagnostics: These tests are
very sensitive, fast, and specific, but they cannot distinguish contaminants,
generally do not provide sensitivity data, and are expensive.

• Stool transplant: FMT is the best treatment for relapsing
CDI. Questions remain about the number of previous relapses before using this
treatment (typically, it is used after two), the source of donor stool, and the
method of insertion.

• Global travelers: Be alert to prevent infections in
persons going to areas with malaria, chikungunya, and dengue (all of these
diseases had US records for imported cases in the past 2 years).

• Hepatitis C: Because this disease is now curable, there is
a new emphasis on diagnostic testing of any patient with standard risks,
unexplained abnormal liver function tests, and belonging to the 1945-1965 birth
cohort ("baby boomers").

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We know that there will be epidemics, but the mystery is what type and where. Particularly concerning from 2014 is chikungunya, with > 600,000 cases in the Caribbean and 240 cases in the United States, including some that were not related to travel; this indicates that mosquito transmission is taking place in Florida, where chikungunya seems likely to become endemic.